Cancers are the most frequent type of human malignancies, and the fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases.
S100A7 protein (Psoriasin) is a member of the S100 family of calcium-binding proteins which was initially identified as an over-expressed protein in the skin of patients with psoriasis. In normal cells the expression levels of S100A7 protein are very reduced, however high levels of expression of said protein can be found in tumor cells derived from for example, breast cancer, skin cancer, stomach cancer, bladder cancer and also head and neck cancer.
In breast cancer, the expression levels of S100A7 protein are very high in stage of pre-invasive tumors such ductal carcinoma in situ and are reduced in the acquisition of invasive phenotype. The persistently high expression level of S100A7 in invasive breast cancer is a poor prognosis factor in cancer patients. This correlation has also been demonstrated in skin cancer patients among other cancers.
The intracellular and extracellular location of S100A7 has been demonstrated and its expression can be detected in the cytoplasm and sometimes, in the cellular nucleus. The entire mechanism of action of said protein is still unknown although the Jab1 protein has been identified as S100A7 binding-protein.
The S100A7 protein has a proinflammatory function acting as chemotactic agent for immune cells recruiting. In this sense, the positive correlation between high expression of S100A7 and immune cells infiltration in tumoral stroma and also with metastatic potential has been described.
S100A7 plays an important role in breast cancer progression by promoting angiogenic response. When S100A7 is secreted by mammary epithelial cells, said protein induces an increase in endothelial cell proliferation acting via RAGE receptor (receptor for advanced glycation end products).
The S100A7 protein is also over-expressed in a large number of hyperproliferative and inflammatory skin diseases including atopic dermatitis.
It has been demonstrated that pro-inflammatory action of S100A7 is carried out by its interaction with RAGE receptor. Said interaction is involved in immune cells recruiting and also induces cytokine and chemokine production by neutrophils which contribute to inflammatory process.
It has been disclosed that silencing S100A7 by using stable short hairpin RNA (shRNA) in a human tumor cell line increases anchorage-independent growth, cell motility and invasion in vitro, while decreasing tumorigenicity in vivo (Krop et al., Cancer Res., 2005; 65:11326-11334). However, these effects are not due to the direct inhibition of S100A7 activity, but rather to decreased VEGF and increased MMP-13 levels.
Therefore, there is a need in the art to provide new therapeutic approaches for the treatment of cancer, particularly for the treatment of metastatic cancer, targeting the S100A7 protein.
In addition, at a diagnostic level, S100A7 can be considered a good marker in the differentiation progress of a normal cell towards a tumor cell, and therefore is a good biomarker in the cytological examination of tumors (Barbieri M R. et al., BMC Res Notes, 2011; 4(1): 494). However, the detection of the expression of S100A7 in cancerous tissue presents the drawback of requiring a patient biopsy. Therefore, there is a need in the art to provide a simpler and less invasive method for the clinical diagnosis of cancer by means of detecting the levels of S100A7 in a subject.